Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer
<p>Abstract</p> <p>Background</p> <p>Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that l...
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| Format: | Article |
| Language: | English |
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BMC
2009-08-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/282 |
| _version_ | 1811279215035678720 |
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| author | Rems Miran Štor Zdravko Volavšek Metka Berginc Gašper Mlakar Vid Glavač Damjan |
| author_facet | Rems Miran Štor Zdravko Volavšek Metka Berginc Gašper Mlakar Vid Glavač Damjan |
| author_sort | Rems Miran |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development.</p> <p>Methods</p> <p>We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the <it>KRAS </it>mutation was investigated.</p> <p>Results</p> <p>We detected significant previously undescribed underexpression in CRC for genes <it>SLC26A3</it>, <it>TPM1 </it>and <it>DCN</it>, with a suggested tumour suppressor role. We also describe the correlation between <it>TPM1 </it>and <it>DCN </it>expression and the presence of <it>KRAS </it>mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the <it>TPM1 </it>gene in one case of CRC, but no deletions of <it>DCN </it>and <it>SLC26A3 </it>were found.</p> <p>Conclusion</p> <p>Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the <it>TPM1 </it>gene in a case of CRCs without <it>KRAS </it>mutations, showing that <it>TPM1 </it>might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the <it>TPM1 </it>gene. On the other hand, the correlation of <it>DCN </it>underexpression with the presence of <it>KRAS </it>mutations suggests that <it>DCN </it>expression is affected by the presence of activating <it>KRAS </it>mutations, lowering the amount of the important tumour suppressor protein decorin.</p> |
| first_indexed | 2024-04-13T00:50:43Z |
| format | Article |
| id | doaj.art-17ddca94bd67414ea8b1400527460b81 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T00:50:43Z |
| publishDate | 2009-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-17ddca94bd67414ea8b1400527460b812022-12-22T03:09:53ZengBMCBMC Cancer1471-24072009-08-019128210.1186/1471-2407-9-282Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancerRems MiranŠtor ZdravkoVolavšek MetkaBerginc GašperMlakar VidGlavač Damjan<p>Abstract</p> <p>Background</p> <p>Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development.</p> <p>Methods</p> <p>We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the <it>KRAS </it>mutation was investigated.</p> <p>Results</p> <p>We detected significant previously undescribed underexpression in CRC for genes <it>SLC26A3</it>, <it>TPM1 </it>and <it>DCN</it>, with a suggested tumour suppressor role. We also describe the correlation between <it>TPM1 </it>and <it>DCN </it>expression and the presence of <it>KRAS </it>mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the <it>TPM1 </it>gene in one case of CRC, but no deletions of <it>DCN </it>and <it>SLC26A3 </it>were found.</p> <p>Conclusion</p> <p>Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the <it>TPM1 </it>gene in a case of CRCs without <it>KRAS </it>mutations, showing that <it>TPM1 </it>might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the <it>TPM1 </it>gene. On the other hand, the correlation of <it>DCN </it>underexpression with the presence of <it>KRAS </it>mutations suggests that <it>DCN </it>expression is affected by the presence of activating <it>KRAS </it>mutations, lowering the amount of the important tumour suppressor protein decorin.</p>http://www.biomedcentral.com/1471-2407/9/282 |
| spellingShingle | Rems Miran Štor Zdravko Volavšek Metka Berginc Gašper Mlakar Vid Glavač Damjan Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer BMC Cancer |
| title | Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer |
| title_full | Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer |
| title_fullStr | Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer |
| title_full_unstemmed | Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer |
| title_short | Presence of activating <it>KRAS </it>mutations correlates significantly with expression of tumour suppressor genes <it>DCN </it>and <it>TPM1 </it>in colorectal cancer |
| title_sort | presence of activating it kras it mutations correlates significantly with expression of tumour suppressor genes it dcn it and it tpm1 it in colorectal cancer |
| url | http://www.biomedcentral.com/1471-2407/9/282 |
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